1. Early Detection of Severe Sepsis Robin Horsley, AGACNP-BC, RRT, VA-BC Adult Geriatric Acute Care Nurse Practitioner Sheridan Memorial Hospital Intensive Care

2. Sepsis  Sepsis is diagnosed in over one million patients each year in the United States.  An estimated 20.3 billion or 5.2 percent of the total cost of all hospitalizations and the most expensive condition treated in the year 2011.  High mortality rate.  Over the age of 65 (include differential of sepsis)

3. Surviving Sepsis and Septic Shock  Mortality rates associated with sepsis  28-50% for severe sepsis  50-60% for septic shock  Severe sepsis is the leading cause of death in the non-coronary ICU  Sepsis kills approximately 1,400 people worldwide every day 2013 NYS DOH issues a mandate for all hospitals to produce clinical care guidelines for evidence-based recognition and treatment of sepsis. Adult and Pediatric treatment protocols for both ED and inpatient. Education of hospital staff: Physician/Resident, RN, Pharm, Laboratory. Data submission for public reporting of outcomes.

5. Severe Sepsis Recommendations Adult and Pediatric Evidence-based Studies 1. Early Detection 2. Early Treatment Sepsis Resuscitation Bundle 3. Monitor reliability and outcomes

6. Surviving Sepsis Campaign  Acronym  LEADER  Learn about sepsis and quality improvement  Establish a baseline to show that improvement is necessary (start collecting data) show any gaps in care  Ask for buy-in from leadership and seek support from stakeholders (providers, quality councils, Chief Medical officer.  Develop institution specific Protocol comprising all bundle elements  Educate stakeholders  Remediate errors and anticipate obstacles along the way

7. Severe Sepsis Bundles  The Severe Sepsis Bundles area a series of evidence-based therapies that, when implemented together, will achieve better outcomes than if implemented individually.  3 hour Bundle implementation  6 hour Bundle implementation  Other selected therapies recommended by the 2012 Surviving Sepsis Campaign:  Blood Product Administration  Maintain Adequate Glycemic Control  Mechanical ventilation of Sepsis-induced Acute Respiratory Distress syndrome  Sedation, analgesia, and neuromuscular Blockade  Deep Vein Thrombosis and peptic ulcer disease prophylaxis

8. Society of Critical Care Medicine  The SCCM reports finding of a task force charged with putting forth new recommendations for sepsis to providers.  The group recommendations move forward the new definitions of sepsis and septic shock.  They provide new recommendations for providers in the quick assessment and treatment.  Suggested method to determine organ dysfunction is: Sequential(Sepsis Related) organ failure assessment (SOFA)

9. Defining the septic picture SIRS (Systemic inflammatory response syndrome): The clinical syndrome that results from a deregulated inflammatory response syndrome or to a noninfectious insult. Sepsis: SIRS that is secondary to infection that has been diagnosed clinically. Positive cultures add to the validity but are not required for the diagnosis. Severe Sepsis: Sepsis plus at least one of the signs of hypo perfusion or organ dysfunction that is new, and not explained by other known etiology of organ dysfunction. Septic Shock: Severe sepsis associated with refractory hypotension (BP 4.0 mmol/L.

10. Further recommendations  Physicians should be looking for organ dysfunction every time the suspect infection.  Conversely they should be looking for infection when a patient presents with organ dysfunction.

11. Quick SOFA or qSOFA  Consists of 3 simple tests that clinicians can do at bedside with patients who are at risk for sepsis.  The qSOFA assessment directs physicians to look for these warning signs.  An alteration in Mental Status  A decrease in systolic blood pressure less than 100 mm Hg  A respiratory rate of > 22 breaths/min.

12. Evaluating Severe Sepsis  Q1: Suspected infection - clinical judgment to determine if there is a new potential site of infection.  Q2: Signs of SIRS – two signs and symptoms of SIRS based on vitals and recent lab results.  Q3: Organ dysfunction – often discovered by an abnormal serum lactate value

13.  Data indicate that patients with two or more of these conditions are at a significantly greater risk for prolonged ICU stay (3 or more days) or to die in the hospital.  For these patients the task force recommends that clinicians investigate further for organ dysfunction, initiate or escalated therapy as appropriate and to consider referral to critical care or increase the frequency of monitoring.

14. HRET HEN 2.0 http://www.hret-hen.org/ Hospital Engagement Network HRET Mission Transforming health care through research and education. HRET Vision Leveraging research and education to create a society of healthy communities, where all individuals reach their highest potential for health

15. Since the last Sepsis Change Package by HRET, the science has evolved, and there are key changes.  Early goal-directed therapy for volume replacement via formal algorithms has been shown by the ARISE8, ProMISe9 and ProCESS10 studies to not offer a clinical advantage.  The Surviving Sepsis Campaign has changed the 6-hour bundle, updating the assessment of volume status. The 6-hour bundle no longer requires the use of central venous pressure lines or ScvO2 if early recognition of sepsis and timely antibiotic administration has occurred. Instead these two modalities are one of the optional methods to assess volume. No changes have been made to the 3-hour bundle.  New information suggests that hypotonic fluids, when used for resuscitation and maintenance volume therapy, place the acutely ill patient at significant risk for hyponatremia. Isotonic fluid should be used. Data is insufficient to recommend balanced versus unbalanced isotonic solutions.11

16. Measurement Additionally, in 2014 the Centers for Medicare & Medicaid Services added a requirement for hospitals to report post-operative sepsis as a Hospital Acquired Condition. The measure used comes from the Agency for Healthcare Research and Quality Patient Safety Indicator 13.12 CMS recently added the first National Core Measure for Sepsis beginning October 2015 measuring compliance with the 3-hour and 6-hour bundle interventions to reduce sepsis mortality.

17. 1717 © Cerner Corporation. All rights reserved. This document contains Cerner confidential and/or proprietary information belonging to Cerner Corporation and/or its related affiliates which may not be reproduced or transmitted in any form or by any means without the express written consent of Cerner. Prognostic effects of organ dysfunction in severe sepsis

18. 1818 © Cerner Corporation. All rights reserved. This document contains Cerner confidential and/or proprietary information belonging to Cerner Corporation and/or its related affiliates which may not be reproduced or transmitted in any form or by any means without the express written consent of Cerner. Prevalence of hospital mortality associated with severe sepsis

19. Adult Sepsis/Severe Sepsis Criteria  SIRS Hyperthermia >38°C or Hypothermia <36°C Acutely Altered Mental Status Tachycardia >90 bpm PCO2 >32 mmHg Tachypnea >20 bpm Leukocytosis (>12,000 µL-1) or Leukopenia ( 10% bands Hyperglycemia (>120 mg/dl) in the absence of diabetes (2 or more of these with known or suspected infection diagnosis of sepsis placed)  Signs of hypo perfusion or organ dysfunction: Hypotension (<90/60 or MAP <65) Lactate >4 (severe sepsis) Areas of mottled skin or capillary refill >3 seconds Creatinine >2.0 mg/dl Disseminated intravascular coagulation (DIC) Platelet count <100,000 Acute renal failure or urine output <0.5 ml/kg/hr for at least 2 hours Hepatic dysfunction as evidenced by Bilirubin >2 or INR >1.5 Cardiac dysfunction Acute lung injury or ARDS  (Severe sepsis). The final stage is septic shock, which is defined as severe sepsis with persistent hypotension, signs of end-organ damage, or lactate levels than 4mmol/L.

20. Pediatric Sepsis/Severe Sepsis Criteria Heart Rates, Beats/Min Leukocyte Count Age GroupTachycardiaBradycardia Respiratory Rate Leukocytes X 103/mm 3b,c. Hypotension, mm Hg 0 days to 1 wk>180<100>60>34<59 1 wk to 1 mo>180<100>50>19.5 OR <5<75 1 mo to 1 yr>180<90>35>17.5 OR <5<75 3-6 yrs>140Not applicable>30>15.5 OR <6<75 6-12 yrs>130Not applicable>20>13.5 OR <4.5<83 13 to <18 yrs>110Not applicable>20>11 OR <4.5<90 Signs of hypoperfusion or organ dysfunction: Hypotension < 5 th percentile for age or systolic BP < 2 SD below normal age for age Need for vasoactive drug to maintain BP in normal range (dopamine >5 μg/kg/min or dobutamine, epinephrine at any dose) Two of the following: Unexplained metabolic acidosis: base deficit > 5.0 mEg/L Increased arterial lactate > 2 times upper limit of normal Oliguric: urine output <0.5 mL/kg\hr Prolonged capillary refill: > 5 secs Core to peripheral temperature gap > 3°C PAO 2/ FIO 2 <300 in absence of cyanotic heart disease or preexisting lung disease PaCO 2 >65 torr or 20 mm Hg over baseline PaCO 2 Proven need for >50% FiO 2 to maintain saturation ≥ 92% Need for nonelective invasive or noninvasive mechanical ventilation Glasgow Coma Score ≤11 Acute change in mental status with a decrease in Glasgow Coma Score ≥3 points from abnormal baseline Platelet count < 80,000/mm 3 or a decline of 50% in platelet count from highest value recorded over the past 3 days (for chronic hematology/oncology patients) International normalized ratio >2 Serum creatinine ≥ 2 times upper limit of normal for age or 2- fold increase from baseline creatinine Total bilirubin ≥4 mg/dL (not applicable for newborn) ALT 2 times upper limit of normal for age

21. How do we manage sepsis and septic shock? 1) Investigate and treat sepsis Try to find and treat source Early blood cultures Start antibiotics ASAP, ideally within 1 hour and after cultures taken 2) Assess extent of end organ hypo perfusion and improve oxygen delivery (early goal directed therapy)

22. Resuscitation Bundle 3-hour and 6-hour Bundle Division 3-hour Bundle – Actions to be taken within the first 3 hours of resuscitation from initial recognition for adults and within 60 minutes from initial recognition for pediatric patients. 6 – hour Bundle – Actions to be taken within the first 6 hours of resuscitation from initial recognition for adults and within 60 minutes from initial recognition for pediatric patients. Two treatment track – invasive or non- invasive Track followed is based on the criticality and initial response to hemodynamic measures.

23. Resuscitation Bundle 3-hour Bundle Serum lactate measured within 3 hours of presentation in adults Blood cultures obtained prior to antibiotic administration; additional cultures to determine potential site of infection Early and appropriate broad-spectrum antibiotic administration within 3 hour for ED presentation. within 1 hour for floors/ICU presentation. In the event of hypotension and/or a lactate >4 mmol/L, deliver a minimum of 30 ml/kg of fluids in adults. a minimum of 20mL/kg of fluids in children. Best Practice Treatment of Severe Sepsis

24. Resuscitation Bundle 6-hour Bundle Vasopressor therapy for persistent hypotension (MAP <65 in adults) despite initial fluid administration Re-measure lactate if the initial value was elevated Invasive A central venous catheter capable of measuring CVP (original study and recommendation. New recommendations; no longer requires the use of CVP or ScvO2 if early recognition of sepsis and timely antibiotics administration has occurred. Non-invasive Contraindications for invasive track Trending of lactate levels to gauge fluid response Best Practice Treatment of Severe Sepsis

25.  Sepsis care bundles  3 hour bundle completed within 3 hours of presentation  6 hour bundle all task completed within 6 hours of presentations.  The CLOCK BEGINs once the patient meets SIRS criteria.  For patients who present to the Emergency department, this means “zero” hour is at presentation to triage.  For inpatients, the “zero” hour is when the patients vital signs first meet SIRS criteria, regardless of when it was recognized and treated.  We are held to this standards by Centers for Medicare as a Core measure.

26. Fluid Challenge What is the difference between an infusion and a challenge? Suggests hypotonic fluids, when used for resuscitation and maintenance volume therapy, place the acutely ill patient at significant risk for hyponatremia. Isotonic fluid should be used. 250 to 500 ml colloid (or blood products) 500 to 1000ml LR [NOT 5% dextrose] As fast a possible (with pressure bag) You at the bedside

27. Markers of perfusion What are they?  Clinical signs  Warm skin, conscious level, u/o  Hemodynamic variables  CVP  Bloods  Serum Lactate  ScvO2

28. CVP What does it mean? Starling’s Law Estimate of LVEDV (i.e. preload) Not always a good correlation with volume-responsiveness However if low strongly suggestive of hypovolemia

29. Lactate What does it mean?  Increased production (anaerobic glycolysis)  Tissue hypo perfusion  Tissue dysoxia  Reduced metabolism  Hepatic  Renal  1-2 is a normal, >2 is bad, >4 is very bad

30. ScvO2 What does it mean?  Balance between oxygen delivery and consumption (VO2)  Fick principle  ScvO2 = SaO2 - VO2  CO  Target > 70%

31. Surviving Sepsis targets of fluid resuscitation What are they?  SBP  MAP  CVP  U/o  Lactate  ScvO2  HCt

32. Further Management What else can be done?  Low tidal volume ventilation  Steroids in septic shock  Activated Protein C  Glycemic control  Stress ulcer prophylaxis  Thromboprophylaxis  Sedation scoring / holds etc.

33. Case 1 16:00: An 81 year-old woman was admitted to the emergency department with nausea, vomiting and hypotension. She has a history of hypertension, Type II Diabetes, renal insufficiency and dementia. Home medications: aspirin, furosemide, tolterodine tartrate, memantine, Valsartan, metformin, Lovastatin and niacin. On admission she presented with low grade fever 37.9, a blood pressure (BP) of 60/30 and heart rate (HR) of 130. Lab results on admission included: WBC 16.7k cells/ml, Hgb 9.2gm/dl, creatinine 1.6 mg/dl, albumin 2.7mg/dL, sodium 135 mEq/L and potassium 4.7 mEq/L. Abdominal CT was within normal limits (WNL) What are missing on labs that would be helpful? What other diagnostic studies? What is my differential diagnoses?

34.  UA WBC’s greater than 20  Positive for nitrates  Lactic acid 4.2  Chest x-ray COPD no infiltrate

35. 3535 © Cerner Corporation. All rights reserved. This document contains Cerner confidential and/or proprietary information belonging to Cerner Corporation and/or its related affiliates which may not be reproduced or transmitted in any form or by any means without the express written consent of Cerner. What would be our first line treatment? The patient was treated with 2 liters of IV normal saline but her BP remained low. Dopamine was added and at a dose greater than 5mcg/kg/min her HR increased to 150 bpm and the dose was reduced to 3mcg/Kg/min. Dobutamine was added at 7mcg/kg/min. The patient was diagnosed with septic shock and admitted to the Intensive Care Unit (ICU). Treatment plan was fluids, pressors as needed and antibiotic treatment. What might have been a better treatment for her hypotension? What is your diagnosis?

36. Case 2  44 year old male with altered mental status.  Been sick with a cough for about 2 weeks according to wife.  She was unable to arouse him this morning and called 911.  In the ER his Vital signs were as follows: HR 122, RR 10, BP72/40, oxygen saturations 84%. GCS 8. He is unresponsive to verbal stimuli. What is my next move? What is in my differential?

37. Diagnostics  Labs:  WBC 2.5  HBG 9.2  HCT 27  Lactic Acid 6.2  BUN 123  Creatinine 4.2  AST 200  ALT 240  Bil 3.0  Chest X-ray: ground glass appearance with right middle and lower lobe infiltrate. Bilateral pleural effusions. ET tube in good position.  CT head: Normal

38. Now what is my diagnosis?  Initial Resuscitation  1. hypotension persisting after initial fluid challenge or blood lactate concentration ≥ 4 mmol/L. Goals during the first 6 hrs of resuscitation:  a) Central venous pressure 8–12 mm Hg  b) Mean arterial pressure (MAP) ≥ 65 mm Hg c) Urine output ≥ 0.5 mL/kg/hr d) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively (grade 1C).  2. In patients with elevated lactate levels targeting resuscitation to normalize lactate

39. Newer guidelines  1. Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C) as the goal of therapy (broad then narrow once you have definite source)  Fluid Therapy of Severe Sepsis  1. Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (grade 1B).  2. Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock (grade 1B).  3. Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (grade 2C).  4. Initial fluid challenge in patients with sepsis-induced tissue hypo perfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid  may be needed in some patients (grade 1C).  5. Fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic (eg, change in pulse pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables (UG).

40.  H. Vasopressors  1. Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg (grade 1C).  2. Norepinephrine as the first choice vasopressor (grade 1B).  3. Epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B).  4. Vasopressin 0.03 units/minute can be added to norepinephrine (NE) with intent of either raising MAP or decreasing NE dosage (UG).  5. Low dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension and vasopressin doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents) (UG).  6. Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk of tachyarrhythmia's and absolute or relative bradycardia) (grade 2C).

41. Sheridan Memorial Hospital -Reduced mortality rates ~43 % from 20.00% to 11.21% since go live in December 2014. -~71% increase in documented diagnosis of Sepsis

42. Questions

43. Select References – Available upon request Rivers et al. Early Goal-directed therapy in the treatment of severe sepsis and septic shock. N Eng J Med, Vol. 345, No. 19. November 8, 2001. Townsend et al. Reducing Mortality in Severe Sepsis: The Surviving Sepsis Campaign. Clin Chest Med. 29 (2008) 721-733 Shapiro et al. Serum Lactate as a Predictor of Mortality in Emergency Department Patients With Infection. Annals of Emerg Med. May 2005, V45, No.5. Jones et al. Lactate Clearnace vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial. JAMA. 2010;303(8):739-746. Nguyen et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004;Vol. 32, No. 8. Micek et al. Before-after study of a standardized hospital order set for the management of septic shock. Crit Care Med. 2006;Vol. 34, No. 11. Dellinger et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008; Vol. 36, no.1. Berry et al. Assessing Tissue Oxygenation. Crit Care Nurse. Vol 22, No. 3, June 2002. Howell et al. Occult hypoperfusion and mortality in patients with suspected infection. Intensive Care Med. (2007) 33:1892-1899. Bakker et al. Don’t take vitals, take a lactate. Intensive Care Med. (2007) 33:1863-1865. Angus et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit care Med. 2001; Vol. 29, No. 7. Donnino et al. Cryptic septic shock: A sub-analysis of early, goal-directed therapy. Chest (2003); 124(4): 905.